|
KMID : 0043320180410010035
|
|
Archives of Pharmacal Research
2018 Volume.41 No. 1 p.35 ~ p.45
|
|
|
Design, synthesis and evaluation of alkylphosphocholine-gefitinib conjugates as multitarget anticancer agents
|
|
Alam Maqusood
Hassan Ahmed H. E.
Kwon Yeong-Ho
Lee Hyo-Jong
Kim Nam-Yong
Min Kyung-Hoon
Lee Sang-Yoon
Kim Dong-Hyun
Lee Yong-Sup
|
|
|
Abstract
|
|
|
|
The evolving resistance to the currently used chemotherapeutic agents requires continuous efforts to develop new anticancer agents overcoming resistance and with lower side effects. Polypharmacology via designing a single molecule intercepting multiple signaling pathways is more effective than targeting a single one. Several alkylphosphocholines show anticancer activity via inhibition of Akt phosphorylation. On the other hand, several molecules having quinazoline scaffold elicit anticancer activity through inhibition of epidermal growth factor receptor (EGFR) tyrosine kinases. We report our efforts to develop alkylphosphocholines-gefitinib conjugates as multitarget anticancer agents. The antiproliferative activities of the newly synthesized compounds were evaluated against cell lines representing lung, breast, liver and skin cancers. In addition, the capability of the newly synthesized compounds to inhibit Akt phosphorylation and EGFR tyrosine kinases were determined. The results emphasized the influence of the linkers’ length on the elicited bioactivity. The long chain linkers possessing conjugates were more active regarding both of the elicited antiproliferative effect and inhibition of Akt phosphorylation, while maintained the ability to inhibit EGFR tyrosine kinases. Their cytotoxic activities were superior or comparable to erlotinib and miltefosine.
|
|
|
KEYWORD
|
|
|
Alkylphosphocholines, Gefitinib, Akt phosphorylation inhibitors, EGFR tyrosine kinase inhibitors, Antiproliferartive agents
|
|
|
FullTexts / Linksout information
|
|
|
|
|
|
Listed journal information
|
|
  
|